TABLE 2.
Study Outcomes: Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children
| Outcome | Study Results | Certainty of the Evidence (quality of evidence) | Plain Text Summary |
|---|---|---|---|
| Overall response rate (primary outcome)a | ORR: 75%a (95% CI, 61% to 85%; pre-established lower boundary of 30% ruled out); 13% complete response (95% CI, 6% to 25%); 62% partial response (95% CI, 49% to 75%); 13% stable disease (95% CI, 6% to 25%); 9% progressive disease (95% CI, 3% to 20%); 4% early withdrawal because of clinical deterioration (95% CI, 0.5% to 13.5%) | Low (1, 2) | Larotrectinib may improve overall response for patients with TRK fusion-positive tumors |
| Progression-free survival | 55% progression-free at 1 year (95% CI, 42% to 67%) | Low (1, 2) | Larotrectinib may improve progression-free survival for patients with TRK fusion-positive tumors |
| Most common grade 3–4 adverse events | 1,038 events occurred among 55 patients (93% grade 1 or 2; 7% grade 3 or 4): | Very low (1) | Larotrectinib may result in adverse events for patients with TRK fusion-positive tumors |
| Anemia (11%) | |||
| Increased level of ALT or AST (7%) | |||
| Weight increase (7%) | |||
| Decreased neutrophil count (7%) | |||
| Drug reductions or discontinuations | 15% had dose reductions related to adverse events; no discontinuations as a result of drug-related adverse events were recorded | Very low (1) | Larotrectinib may result in dose reductions for patients with TRK fusion-positive tumors |
NOTE. Results from Drilon et al.17 (1) Downgrade: commercially funded; indirectness: locally advanced included. (2) Upgrade: large magnitude of effect. Population: Fifty-five patients with TRK fusion-positive locally advanced or metastatic tumors, including 1 patient with pancreatic cancer. Intervention: Larotrectinib (20 patients treated in dose-escalation study and 35 treated at a therapeutic dose of 100 mg orally twice daily). Comparator: no comparator arm. ALT, alanine aminotransferase; AST, aspartate aminotransferase.